GENOMICS AND HIGH THROUGHPUT SCREENING SHARED RESOURCE: PROJECT SUMMARY The Genomics and High Throughput Screening Shared Resource (GHTSSR) is jointly operated by the Herbert Irving Comprehensive Cancer Center (HICCC) and the Judith H. Sulzberger Columbia Genome Center in the Department of Systems Biology. This state-of-the-art sequencing and high throughput screening facility provides HICCC investigators with access to advanced Next Generation Sequencing (NGS) technologies and supports chemical and forward genetic high throughput screens. Services provided include: (1) RNA and DNA NGS, (2) single-cell RNA-seq, (3) high throughput and high-content microscopy-based screening of chemical, RNAi, and cDNA libraries. Each of these platforms is seamlessly integrated into a centralized facility in support of innovative NGS-based high throughput screening approaches developed in the Department of Systems Biology for the identification of cancer driver master regulators and personalized cancer therapies. Directed by Olivier Couronne, PhD, MBA, the GHTSSR is broadly used and highly regarded by HICCC investigators for its reliability, advanced capabilities, and a high-level of technical innovation. The GHTSSR sequencing services (RNA-seq, genome wide DNA [whole exome, whole genome, ChIPseq, and ATAC-seq library) and targeted DNA sequencing) are of high-quality, readily accessible, affordable, and are performed in a timely manner. Comprehensive single-cell RNA-seq services make this complex technology highly accessible and a critical resource for HICCC Research Programs studying tumor heterogeneity and plasticity, and the tumor immune and microenvironment. Similarly, high throughput screen platforms supported are tailored to meet the specific needs of HICCC investigators and include innovative sequencing- based high throughput screen technologies such as PLATE-Seq that are not available commercially or at other academic centers. Highly qualified personnel in the GHTSSR facilitate effective use of advanced technologies supporting the research portfolio of HICCC members. The GHTSSR will continue to support and incorporate high-value, cost-effective, and innovative sequencing and high throughput screen platforms, technologies, and services, as well as training and consulting for HICCC members. During the current project period (2014-2019), the capabilities of the GHTSSR were utilized by 77 HICCC, supported key data and insights for 56 peer-reviewed publications, including 31 in journals with impact factor >10, of which 18 were in journals with an impact factor >20 (e.g., Nature, Nature Genetics, Nature Medicine), and currently supports research in 56 NIH-funded grants, 30 from NCI.